Acute Exercise Intervention Combined with Metformin’s Influences on Glucose Homeostasis in T2D Mice

Abstract

PURPOSE: The aim of our investigation was to determine the effects of different ways of acute exercise intervention combined with high dose of metformin on glucose homeostasis and its relative molecular mechanisms in type 2 diabetic mice. METHODS: 4-week high fat diet (HFD) and one-time Streptozocin (100mg/kg) intraperitoneal injection were used for building T2D mice. 24 mice were divided into normal control (NC), normal acute resistance training (NCR) and normal acute endurance training (NCE) group, all n=8, fed in normal chow. Finally 48 mice were developing T2D and divided into diabetic control (DC), diabetic acute resistance training (DCR), diabetic acute endurance training (DCE), high dose of metformin (200mg/kg) control (HMC), metformin combined with acute resistance training (HMR) and metformin combined with acute endurance continuous training (HME) group, all n=8. RESULTS: The two ways also enhanced blood glucose and lipid metabolism in T2D mice. Compared to HMC group, hepatic G6Pase mRNA expression in HMR and HME group was significantly escalated and hepatic FBP1 mRNA expression of both groups were significantly declined. Compared to HMC group, hepatic GLUT2 and Gck mRNA expression in HMR and HME group showed opposite trends, one was down and the other was up. Compared to HMC group, hepatic PEPCK mRNA expression in HMR group mice was notably raised and hepatic AMPKα2, PGC-1α and CREB mRNA expression in HMR and HME group mice were notably increased and only hepatic AMPKα1 mRNA expression in HMR group was significantly increased. CONCLUSIONS: Acute resistance training (ART) and acute endurance training (AET) combined with metformin can effectively improve glucose homeostasis in T2D mice. And the two ways can improve blood glucose and lipid metabolism in T2D mice. ART combined with metformin was better to improve glucose homeostasis and inhibit hepatic gluconeogenesis relative mRNA expression in T2D mice probably via the signaling pathway of AMPKα-PGC-1α-CREB.